62 research outputs found
Untersuchungen zur ErnÀhrungsökologie benthischer Invertebraten im Makrophytensystem : ein marin-limnischer Ansatz
In einem zweijĂ€hrigen Monitoringprogramm wurde die Zusammensetzung der Makroinvertebratengemeinschaften eines marinen (Zostera marina, Seegras) und eines limnischen (Potamogeton perfoliatus, Laichkraut) Makrophytensystems monatlich erfasst. Diese Freilanddaten bildeten die Grundlage fĂŒr umfangreiche Laboruntersuchungen. In Mesokosmenversuchen wurden die intra- und interspezifischen Wechselwirkungen von marinen und limnischen Amphipoden, Isopoden und Gastropoden untersucht. In einem weiteren Versuch konnten saisonalen Unterschiede in der PrĂ€ferenzabfolge von marinen und limnischen Dekapoden, Amphipoden und Isopoden bezĂŒglich tierischer und pflanzlicher Nahrungsquellen nachgewiesen werden. Der Einfluss von unterschiedlichen Nahrungsquellen in AbhĂ€ngigkeit unterschiedlicher Dichtekombinationen von potentiellen Nahrungskonkurrenten auf das Biomassewachstum und die Ăberlebensraten von marinen und limnischen Amphipoden und Isopoden wurde in sechswöchigen Aquarienversuchen getestet. Der Einfluss der untersuchten Faktoren auf die Zusammensetzung der Makroinvertebratengemeinschaften in beiden Systemen werden diskutiert
dPGS Regulates the Phenotype of Macrophages via Metabolic Switching
The synthetic compound dendritic polyglycerol sulfate (dPGS) is a pleiotropic acting molecule but shows a high binding affinity to immunological active molecules as L-/P-selectin or complement proteins leading to well described anti-inflammatory properties in various mouse models. In order to make a comprehensive evaluation of the direct effect on the innate immune system, macrophage polarization is analyzed in the presence of dPGS on a phenotypic but also metabolic level. dPGS administered macrophages show a significant increase of MCP1 production paralleled by a reduction of IL-10 secretion. Metabolic analysis reveals that dPGS could potently enhance the glycolysis and mitochondrial respiration in M0 macrophages as well as decrease the mitochondrial respiration of M2 macrophages. In summary the data indicate that dPGS polarizes macrophages into a pro-inflammatory phenotype in a metabolic pathway-dependent manner
A Transcriptome-Led Exploration of Molecular Mechanisms Regulating Somatostatin-Producing D-Cells in the Gastric Epithelium.
The stomach epithelium contains a myriad of enteroendocrine cells that modulate a range of physiological functions, including postprandial secretion of regulatory peptides, gastric motility, and nutrient absorption. Somatostatin (SST)-producing D-cells are present in the oxyntic and pyloric regions of the stomach, and provide a tonic inhibitory tone that regulates activity of neighboring enteroendocrine cells and gastric acid secretion. Cellular mechanisms underlying the effects of regulatory factors on gastric D-cells are poorly defined due to problems in identifying primary D-cells, and uncertainty remains about which stimuli influence D-cells directly. In this study, we introduce a transgenic mouse line, SST-Cre, which upon crossing with Cre reporter strains, facilitates the identification and purification of gastric D-cells, or cell-specific expression of genetically encoded calcium indicators. Populations of D-cells from the gastric antrum and corpus were isolated and analyzed by RNA sequencing and quantitative RT-PCR. The expression of hormones, hormone receptors, neurotransmitter receptors, and nutrient receptors was quantified. Pyy, Gipr, Chrm4, Calcrl, Taar1, and Casr were identified as genes that are highly enriched in D-cells compared with SST-negative cells. Hormone secretion assays performed in mixed gastric epithelial cultures confirmed that SST secretion is regulated by incretin hormones, cholecystokinin, acetylcholine, vasoactive intestinal polypeptide, calcitonin gene-related polypeptide, oligopetides, and trace amines. Cholecystokinin and oligopeptides elicited increases in intracellular calcium in single-cell imaging experiments performed using cultured D-cells. Our data provide the first transcriptomic analysis and functional characterization of gastric D-cells, and identify regulatory pathways that underlie the direct detection of stimuli by this cell type.This work was supported by the Wellcome Trust (WT088357/Z/09/Z and WT084210/Z/07/Z) and the MRC Metabolic Diseases Unit (MRC_MC_UU_12012/3).This is the final version of the article. It first appeared from Endocrine Society via http://dx.doi.org/10.1210/en.2015-1301
Dendritic polyglycerol nanoparticles show charge dependent bio-distribution in early human placental explants and reduce hCG secretion
A thorough understanding of nanoparticle bio-distribution at the feto-maternal
interface will be a prerequisite for their diagnostic or therapeutic
application in women of childbearing age and for teratologic risk assessment.
Therefore, the tissue interaction of biocompatible dendritic polyglycerol
nanoparticles (dPG-NPs) with first- trimester human placental explants were
analyzed and compared to less sophisticated trophoblast-cell based models.
First-trimester human placental explants, BeWo cells and primary trophoblast
cells from human term placenta were exposed to fluorescence labeled, âŒ5ânm
dPG-NPs, with differently charged surfaces, at concentrations of 1 ”M and 10
nM, for 6 and 24âh. Accumulation of dPGs was visualized by fluorescence
microscopy. To assess the impact of dPG-NP on trophoblast integrity and
endocrine function, LDH, and hCG releases were measured. A dose- and charge-
dependent accumulation of dPG-NPs was observed at the early placental barrier
and in cell lines, with positive dPG-NP-surface causing deposits even in the
mesenchymal core of the placental villi. No signs of plasma membrane damage
could be detected. After 24âh we observed a significant reduction of hCG
secretion in placental explants, without significant changes in trophoblast
apoptosis, at low concentrations of charged dPG-NPs. In conclusion, dPG-NPâs
surface charge substantially influences their bio-distribution at the feto-
maternal interface, with positive charge facilitating trans-trophoblast
passage, and in contrast to more artificial models, the first-trimester
placental explant culture model reveals potentially hazardous influences of
charged dPG-NPs on early placental physiology
Influence of alkaline modification on adsorption properties of aluminum oxide
In this work the adsorption capacity of samples A-2-9ĐĄ, A-2-Na-9ĐĄ, A-2-K-9ĐĄ was studied. It was found that alkaline modification leads to an increase in the efficiency of aluminum oxide dehydrators
Pathological consequences of VCP mutations on human striated muscle
*These authors have contributed equally to this work. Mutations in the valosin-containing protein (VCP, p97) gene on chromosome 9p13-p12 cause a late-onset form of autosomal dominant inclusion body myopathy associated with Paget disease of the bone and frontotemporal dementia (IBMPFD). We report on the pathological consequences of three heterozygous VCP (R93C, R155H, R155C) mutations on human striated muscle. IBMPFD skeletal muscle pathology is characterized by degenerative changes and filamentous VCP-and ubiquitin-positive cytoplasmic and nuclear protein aggregates. Furthermore, this is the first report demonstrating that mutant VCP leads to a novel form of dilatative cardiomyopathy with inclusion bodies. In contrast to post-mitotic striated muscle cells and neurons of IBMPFD patients, evidence of protein aggregate pathology was not detected in primary IBMPFD myoblasts or in transient and stable transfected cells using wild-type-VCP and R93C-, R155H-, R155C-VCP mutants. Glutathione S-transferase pull-down experiments showed that all three VCP mutations do not affect the binding to Ufd1, Npl4 and ataxin-3. Structural analysis demonstrated that R93 and R155 are both surface-accessible residues located in the centre of cavities that may enable ligand-binding. Mutations at R93 and R155 are predicted to induce changes in the tertiary structure of the VCP protein. The search for putative ligands to the R93 and R155 cavities resulted in the identification of cyclic sugar compounds with high binding scores. The latter findings provide a novel link to VCP carbohydrate interactions in the complex pathology of IBMPFD. Keywords: VCP; p97; myopathy; cardiomyopathy; IBMPFD Abbreviations: GST = glutathione S-transferase; IBMPFD = inclusion body myopathy associated with Paget disease of the bone and frontotemporal dementia; PBS = phosphate-buffered saline; SDS = sodium dodecyl sulphate; VCP = valosin-containing protei
SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues
Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to
genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility
and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component.
Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci
(eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene),
including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform
genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer
SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the
diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types
Widespread pesticide distribution in the European atmosphere questions their degradability in air
Risk assessment of pesticide impacts on remote ecosystems makes use of model-estimated degradation in air. Recent studies suggest these degradation rates to be overestimated, questioning current pesticide regulation. Here, we investigated the concentrations of 76 pesticides in Europe at 29 rural, coastal, mountain, and polar sites during the agricultural application season. Overall, 58 pesticides were observed in the European atmosphere. Low spatial variation of 7 pesticides suggests continental-scale atmospheric dispersal. Based on concentrations in free tropospheric air and at Arctic sites, 22 pesticides were identified to be prone to long-range atmospheric transport, which included 15 substances approved for agricultural use in Europe and 7 banned ones. Comparison between concentrations at remote sites and those found at pesticide source areas suggests long atmospheric lifetimes of atrazine, cyprodinil, spiroxamine, tebuconazole, terbuthylazine, and thiacloprid. In general, our findings suggest that atmospheric transport and persistence of pesticides have been underestimated and that their risk assessment needs to be improved
Widespread pesticide distribution in the European atmosphere questions their degradability in air
Risk assessment of pesticide impacts on remote ecosystems makes use of model-estimated degradation in air. Recent studies suggest these degradation rates to be overestimated, questioning current pesticide regulation. Here, we investigated the concentrations of 76 pesticides in Europe at 29 rural, coastal, mountain, and polar sites during the agricultural application season. Overall, 58 pesticides were observed in the European atmosphere. Low spatial variation of 7 pesticides suggests continental-scale atmospheric dispersal. Based on concentrations in free tropospheric air and at Arctic sites, 22 pesticides were identified to be prone to long-range atmospheric transport, which included 15 substances approved for agricultural use in Europe and 7 banned ones. Comparison between concentrations at remote sites and those found at pesticide source areas suggests long atmospheric lifetimes of atrazine, cyprodinil, spiroxamine, tebuconazole, terbuthylazine, and thiacloprid. In general, our findings suggest that atmospheric transport and persistence of pesticides have been underestimated and that their risk assessment needs to be improved
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